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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cell 2020 ; 182 (1): 73-84.e16 Nephropedia Template TP
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Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients B Cells #MMPMID32425270
Cao Y; Su B; Guo X; Sun W; Deng Y; Bao L; Zhu Q; Zhang X; Zheng Y; Geng C; Chai X; He R; Li X; Lv Q; Zhu H; Deng W; Xu Y; Wang Y; Qiao L; Tan Y; Song L; Wang G; Du X; Gao N; Liu J; Xiao J; Su XD; Du Z; Feng Y; Qin C; Qin C; Jin R; Xie XS
Cell 2020[Jul]; 182 (1): 73-84.e16 PMID32425270show ga
The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here, we report the rapid identification of SARS-CoV-2-neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1(+) clonotypes, 14 potent neutralizing antibodies were identified, with the most potent one, BD-368-2, exhibiting an IC(50) of 1.2 and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8 A cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody's epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2-neutralizing antibodies could be directly selected based on similarities of their predicted CDR3(H) structures to those of SARS-CoV-neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B cell sequencing in response to pandemic infectious diseases.